MicroRNAs (miRNAs) can function as tumor suppressors and might provide an efficient strategy for annihilating cancer. Specific miRNAs can be reintroduced into tumor cells to complement the loss of tumor suppression activities. The “miRNA replacement therapy” is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that lead to therapeutic responses. Here, we report the development of miRNA delivery formulation using synthesized miR-520e. This formulation proved to be effective either locally or systematically. MiR-520e accumulation becomes evident in tumor cells and then exerts anti-proliferative function. Meanwhile, intravenous delivery of formulated miR-520e does not induce any deregulation in cytokine levels and liver enzymes. Taken together, our results shed new lights on the concept that systematic delivery of synthetic mimics for tumor suppressor miR-520e and provide potential implications for miRNA therapy in clinic.